Cutting through the stress: RNA decay pathways at the endoplasmic reticulum

Franziska Ottens; Sotirios Efstathiou; Thorsten Hoppe

doi:10.1016/j.tcb.2023.11.003

Cutting through the stress: RNA decay pathways at the endoplasmic reticulum

Trends Cell Biol. 2023 Nov 25:S0962-8924(23)00236-2. doi: 10.1016/j.tcb.2023.11.003. Online ahead of print.

Authors

Franziska Ottens¹, Sotirios Efstathiou¹, Thorsten Hoppe²

Affiliations

¹ Institute for Genetics, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
² Institute for Genetics, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital of Cologne, Cologne, Germany. Electronic address: thorsten.hoppe@uni-koeln.de.

PMID: 38008608
DOI: 10.1016/j.tcb.2023.11.003

Abstract

The endoplasmic reticulum (ER) is central to the processing of luminal, transmembrane, and secretory proteins, and maintaining a functional ER is essential for organismal physiology and health. Increased protein-folding load on the ER causes ER stress, which activates quality control mechanisms to restore ER function and protein homeostasis. Beyond protein quality control, mRNA decay pathways have emerged as potent ER fidelity regulators, but their mechanistic roles in ER quality control and their interrelationships remain incompletely understood. Herein, we review ER-associated RNA decay pathways - including regulated inositol-requiring enzyme 1α (IRE1α)-dependent mRNA decay (RIDD), nonsense-mediated mRNA decay (NMD), and Argonaute-dependent RNA silencing - in ER homeostasis, and highlight the intricate coordination of ER-targeted RNA and protein decay mechanisms and their association with antiviral defense.

Keywords: AGO2; ER quality control; RNA degradation; UPR; proteostasis; ubiquitin.

Publication types

Review